Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

Objective:To study the role of autophagy-associated gene regulation FK506 binding protein 1A (FKBP1A) in the regulation of head and neck squamous cell carcinoma (HNSCC).Methods:TCGA was used to analyze the gene expression difference between HNSCC and normal tissues, and the DAVID was employed to perform functional annotation of differently expressed autophagy-associated genes enrichment in HNSCC. Univariate and multivariate Cox regression analysis was used to find genes that were meaningful for the prognosis of HNSCC patients in TCGA; the Gene Expression Comprehensive Database (GEO) was employed to verify the prognosis of the screened gene; the prognosis of HNSCC patients was analyzed by Kaplan-Meier Plotter.Results:Compared with the normal tissues samples, a total of 38 genes significantly changed in HNSCC tissues. These differential genes were mainly distributed in autophagy-associated pathways in biological processes (BP), cellular components (CC) and molecular functions (MF) in GO analysis. Univariate and multivariate Cox regression analysis found that 18 autophagy-associated genes were significantly correlated with the prognosis of HNSCC patients in the TCGA database. Among them, the high-risk genes were verified in the GEO database, and found that FKBP1A was closely related to the prognosis of HNSCC patients. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays showed that the expression of FKBP1A in patients with HNSCC was higher than that of the corresponding adjacent tissues, and was closely related to the stage of HNSCC.Conclusions:This study used integrated bioinformatics methods to study the role of autophagy-associated genes in the occurrence and development of HNSCC. Moreover, the screened biomarker, FKBP1A, is closely related to the prognosis of HNSCC, and provide the theoretical basis for the pathogenesis and potential treatment of HNSCC.

Bovine adenovirus type 3 (BAdV3) is being used in the development of potential vehicles for gene therapy and vectored vaccine. To that end, a more comprehensive description of BAdV3 biology is essential. In this study, we focused on the role of pIX in BAdV3 virion rescue after full-length BAdV3 genome transfection. Initially, pIX deletion or initiation codon mutation abolished the production of progeny virions, which suggested that pIX was essential for the rescue of BAdV3 containing a full-length genome. Moreover, through transfection of a panel of pIX mutant BAdV3 genomes, we observed that the conserved N-terminus and the putative leucine zipper element (PLZP) were essential for virion rescue, whereas the C-terminus following the coiled-coil domain was non-essential. In addition, swap of the PLZP element and its following region of BAdV3 pIX to corresponding domains of human adenovirus type 5 (HAdV5) did not affect virion production, whereas swap of the entire pIX abolished production of progeny virions. We suggest that failure of the full-length BAdV3 pIX swap might be due to species specificity of its N-terminus region before the PLZP element.
Adenoviridae* ; Adenoviruses, Human ; Biology ; Codon, Initiator ; Genetic Therapy ; Genome ; Genome, Viral* ; Leucine Zippers ; Species Specificity ; Transfection* ; Virion*